N.R. Jena - Protection Against Radiation-Induced DNA Damage by Amino Acids: A DFT Study

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      Publication Details (including relevant citation   information):

          J. Phys. Chem. B 2009, 113, 5633.


      Direct and indirect radiation-induced DNA damage is associated   with the formation of radical cations (G•+) and   radical anions (G•−) of guanine, respectively.   Deprotonation of G•+ and dehydrogenation of   G•− generate guanine neutral radical   [G(−H)] and guanine anion [G(−H)],   respectively. These products are of worrisome concern, as they   are involved in reactions that are related to certain lethal   diseases. It has been observed that guanyl radicals can be   repaired by amino acids having strong reducing properties that   are believed to be the residues of DNA-bound proteins such as   histones. As a result, repair of G(−H) and   G(−H) by the amino acids cysteine and tyrosine has   been studied here in detail by density functional theory in both   the gas phase and aqueous medium using the polarized continuum   and Onsager solvation models of self-consistent reaction field   theory. Solvation in aqueous medium using three explicit water   molecules was also studied. Four equivalent tautomers of each the   above radical and anion that will be formed through proton and   hydrogen loss from all of the nitrogen centers of guanine radical   cation and guanine radical anion, respectively, were considered   in the present study. It was found that in both the gas phase and   aqueous medium, normal guanine can be retrieved from its   radical-damaged form by a hydrogen-atom-transfer (HT) mechanism.   Normal guanine can also be retrieved from its anionic damaged   form in both the gas phase and aqueous medium through a   two-electron-coupled proton-transfer (TECPT) mechanism or a   one-step hydrogen-atom- and electron-transfer (OSHET) mechanism.   The present results are discussed in light of the experimental   findings.

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/jp810468m